KCNJ15
Encyclopedia
Potassium inwardly-rectifying channel, subfamily J, member 15, also known as KCNJ15 is a human gene
, which encodes the Kir4.2 protein
.
The existing literature describing KCNJ15 and Kir4.2 is sparse. In spite of some initial channel nomenclature confusion, in which the gene was referred to as Kir1.3 the channel was first cloned from human kidney
by Shuck and coworkers in 1997. Shortly thereafter it was shown that mutation of an extracellular lysine
residue resulted in 6-fold increase in K+ current. Two years later, in 1999, voltage clamp measurements in xenopus
oocytes found that intracellular acidification decreased the potassium current of Kir4.2. Also activation of protein kinase C decreased the current although in a non-reversible fashion. Furthermore it was found that coexpression with related potassium channel Kir5.1
, changed these results somewhat, which the authors concluded was likely to be a result of heterodimerization. Further voltage clamp investigations found the exact pH sensitivity (pKa = 7.1), open probability (high) and conductance of ~25 pS. In 2007 the channel was found to interact with the Calcium-sensing receptor
in human kidney, using a yeast-two-hybrid system. This co-localization was verified at the protein level using both immunofluorescence
techniques and coimmunoprecipitation
of Kir4.2 and the Calcium-sensing receptor
. Also a mutational study of Kir4.2 has demonstrated that removal of a c-terminal tyrosine
increased the K+ current more than 10-fold. Because the channel has a very high open probability, the authors of this last article conclude that this increase is mediated by increased trafficking of the protein to the membrane and not increased single-channel conductance. This same line of reasoning is applicable to the initial work of Derst and coworkers.
with Interleukin 16
.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, which encodes the Kir4.2 protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
.
Function
Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. Kir4.2 is an integral membrane protein and inward-rectifier type potassium channel. Kir4.2 has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Three transcript variants encoding the same protein have been found for this gene.The existing literature describing KCNJ15 and Kir4.2 is sparse. In spite of some initial channel nomenclature confusion, in which the gene was referred to as Kir1.3 the channel was first cloned from human kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
by Shuck and coworkers in 1997. Shortly thereafter it was shown that mutation of an extracellular lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
residue resulted in 6-fold increase in K+ current. Two years later, in 1999, voltage clamp measurements in xenopus
Xenopus
Xenopus is a genus of highly aquatic frogs native to Sub-Saharan Africa. There are 19 species in the Xenopus genus...
oocytes found that intracellular acidification decreased the potassium current of Kir4.2. Also activation of protein kinase C decreased the current although in a non-reversible fashion. Furthermore it was found that coexpression with related potassium channel Kir5.1
KCNJ16
Potassium inwardly-rectifying channel, subfamily J, member 16 is a human gene encoding the Kir5.1 protein.-Further reading:...
, changed these results somewhat, which the authors concluded was likely to be a result of heterodimerization. Further voltage clamp investigations found the exact pH sensitivity (pKa = 7.1), open probability (high) and conductance of ~25 pS. In 2007 the channel was found to interact with the Calcium-sensing receptor
Calcium-sensing receptor
The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...
in human kidney, using a yeast-two-hybrid system. This co-localization was verified at the protein level using both immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
techniques and coimmunoprecipitation
Immunoprecipitation
Immunoprecipitation is the technique of precipitating a protein antigen out of solution using an antibody that specifically binds to that particular protein. This process can be used to isolate and concentrate a particular protein from a sample containing many thousands of different proteins...
of Kir4.2 and the Calcium-sensing receptor
Calcium-sensing receptor
The calcium-sensing receptor is a Class C G-protein coupled receptor which senses extracellular levels of calcium ion. In the parathyroid gland, the calcium-sensing receptor controls calcium homeostasis by regulating the release of parathyroid hormone .-Signal transduction:The release of PTH is...
. Also a mutational study of Kir4.2 has demonstrated that removal of a c-terminal tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
increased the K+ current more than 10-fold. Because the channel has a very high open probability, the authors of this last article conclude that this increase is mediated by increased trafficking of the protein to the membrane and not increased single-channel conductance. This same line of reasoning is applicable to the initial work of Derst and coworkers.
Interactions
KCNJ15 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Interleukin 16
Interleukin 16
Pro-interleukin-16 is a protein that in humans is encoded by the IL16 gene. This gene was discovered in 1982 at Boston University by Dr. David Center and Dr...
.